PROJECT SUMMARY The University of Kentucky Superfund Research Center (UK-SRC) provides a focused, cross-disciplinary research and training environment to address critical human health challenges associated with halogenated organic substance exposures. Four center projects and five cores make up the proposed UK-SRC to further develop research on lifestyle changes (e.g., nutrition and exercise) in addition to two environmental science projects that will focus on the remediation and engineering solutions to this set of problems. Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) and trichloroethylene (TCE) pose significant health risks and enduring remediation challenges, including sites such as the Paducah Gaseous Diffusion Plant, the largest Superfund site in Kentucky. The UK-SRC?s overall focus for this next cycle is the human health impacts of persistent halogenated organics (e.g., PCBs, TCE, and tetrachloroethene (PCE), and in this new cycle of funding, additional questions about per- and polyfluoralkyl substances (PFAS) will be incorporated. Projects covering biomedical research hypothesize that healthy nutrition and exercise components provide a platform to develop primary prevention strategies for diseases associated with environmental toxic insults, while also providing the basis for new risk assessment paradigms. Further, novel iron-based, nano-structured sensing, capture and remediation systems based on biomimetic binding domains and functionalized membrane platforms offer potential for sustainable advances in technical capability for site remediation. The UK-SRC proposes the following goals: 1) to expedite data-driven discovery as facilitated by the Data Management and Analysis Core that will provide insight about biomarkers of exposures to generate new information about the relationship between pollutant exposure, nutrient intake, physical activity and disease risk; 2) to better understand the biochemical, molecular, and cellular mechanisms underlying the toxicity of halogenated organic compounds (i.e., PCBs and PFAS) with a specific focus on chronic inflammatory diseases and windows of susceptibility; 3) to foster informed decisions that expedite clean-up of halogenated organic compounds through advanced material-based technologies, smart filters, and fate and transport science to reduce exposure risks; 4) to promote and interdisciplinary approaches to environmental health science training that accelerate the impact of complex solution-oriented, stakeholder-engaged research aimed at reducing exposures and improving human health; and 5) to engage bi-directionally and provide environmental health programmatic activities to vulnerable, socially-isolated, under-resourced communities in Kentucky, especially Eastern Kentucky (i.e. Central Appalachia), where chronic inflammatory diseases exceed national averages and exposure risks to environmental pollutants are prevalent. Activities will involve community engaged research and an innovative means of integrating projects through the WHY-ENVIRONMENT initiative.